Case Discussion <Brief Presentation> A 77-year-old lady was admitted because of fever and chest pain for one month. A month prior to this hospitalization, she developed fever, chills and concomitant chest pain, located at the left anterolateral chest with a stabbing character initially, and developed into severe, intolerable sharp pain with radiation to the back thereafter. The pain was aggravated by deep inspiration, cough, and swallowing, and was not alleviated by changing position. She has been admitted for this problem while antibiotics were prescribed for several days and the fever subsided. After discharge, she suffered from recurrent fever, chills and aggravating chest pain, accompanied by diaphoresis. She was hospitalized again, and due to the characteristic chest pain and fever, CT scan was performed and revealed saccular aneurysm of the proximal descending aorta with size up to 3 cm. Because previous blood culture yielded Salmonella species, group D (O9), mycotic aneurysm was diagnosed through microbiological and imaging study. Intravenous ceftriaxone 2 g twice per day were started with no delay. Fever, leucocytosis, and CRP improved under antibiotic treatment. Despite 2-week antibiotic management and aggressive blood pressure control, the chest pain was not improved. She was thus referred to our hospital. She denied body weight loss, cough, sputum production, hemoptysis, dyspnea, odynophagia, dysphagia, hoarseness, acid regurgitation or burning sensation, focal limb weakness or pain, syncope, near fainting, arthralgia, skin rash, photosensitivity, or abdominal discomfort. She did not recall any preceding upper respiratory tract infection episode, trauma, dental or urological procedure. Reviewing the past history, she has diabetes and hypertension under regular medical control. She had received left lung lobectomy for solitary pulmonary nodule. No malignancy or tuberculosis was told ever. She had good functional capacity and no further abnormality was noted. She did not smoke or drink. There was no chronic consumption of particular drugs or herbs except the medications for diabetes and hypertension, which included long-acting nifedipine, isosorbide mononitrate, and glipizide. At admission, she appeared acute ill-looking but the consciousness was clear and oriented. The body temperature was 38.3℃, the pulse rate 88 beats/min, and the respiratory rate 20 breaths/min. Pulse oxygenation was 96% under room air. The blood pressure measured at the right arm was 130/80 mmHg, 136/80 mmHg at the right leg, 130/72 mmHg at the left arm and 138/82 mmHg at the left leg. The conjunctivae were pink and the sclerae were anicteric. She had no nuchal rigidity, no goiter, no neck mass and no lymphadenopathy. The jugular vein was not engorged. The chest wall symmetrically expanded. Pulmonary ausculation revealed rales and friction rub over the left lower chest. The point of maximal impulse was localized at the fifth intercostal space and left middle clavicular line. No thrill or heave was noted by palpation. The cardiac auscultation disclosed a grade II/VI pansystolic murmur over apex area without radiation. No S3 or S4 gallop was noted. No frictoin rub was noted. She had soft and flat abdomen with neither tenderness nor rebounding pain. The liver and spleen span were not enlarged. The bowel sound was normoactive. The extremities were freely movable without pitting edema or cyanosis. Except the operation scar over the left lateral chest, she had intact skin, nails and hair. The other physical examinations were unremarkable. The laboratory tests revealed leucocytosis with left shift, and normocytic anemia. The serum CRP level was high. The biochemistry showed normal kidney and liver functional test. No proteinuria, hematuria, pyuria, or active sediment was noted in urinalysis. The coagulation profile was normal. Blood, urine and stool were collected for further microbiological study. The detailed laboratory data were available in tables below. CT scan was performed again and revealed progression of the disease. There was aortic aneurysmal dilation, 5 cm in size with risk of impending rupture and image character of aortitis. Aortic dissection with partial mural thrombosis, involving aortic arch, left subclivian artery and the descending thoracic aorta was also noted. Echocardiography of the chest and heart revealed only minimal pericardial and pleural effusion. Intravenous ceftriaxone 2 g twice per day was given continuously. Labetalol infusion was applied for BP control. Cardiovascular surgeon was then consulted. She underwent operation 3 weeks after parenteral effective antibiotic treatment. Wide debridement of the infected tissue, and in-situ repair with aorta graft were done. Parenteral ceftriaxone was kept for 4 weeks and followed by oral ciprofloxacin. No recurrent fever episode was ever noted. She was smoothly discharged with oral ciprofloxacin, which was scheduled to be kept for 4 months after operation. <Laboratory data> 1. Hemogram Date WBC RBC HB  HCT  MCV MCH MCHC PLT   K/μL M/μL g/dL  % fL Pg g/dL K/μL 940119 14100 3.68 10.7 32.8 89.1 29.1 32.6 344   Band % Seg % Eos % Baso % Mono % Lym % Aty. Lym % Normob % 0  89 1.5  0.2 5.8 20.5 0 0 2. Biochemistry and electrolyte Date Alb Glo T/D-bil AST ALT ALP LDH BUN Cre   g/dL  g/dL mg/dL U/L U/L U/L U/L mg/dL mg/dL 940119 3.0 3.7 0.31/0.37 30 17 116 593 13.5 0.8 Date UA Na K  Cl Ca TG T-cho CRP AC glu   mg/dL mmol/L mmol/L mmol/L mmol/L mg/dL mg/dL mg/dL mg/dL 940119 6.5 133 4.1   103 1.96 109 75 15.5 165 Date  Iron TIBC Ferritin Folic acid Vit B 12   μg/dl (66-155) μg/dl (275-332) ng/ml ng/ml (3.1-12.4) Pg/ml (239-931) 940121 23 134 401 4.27 442 3. Coagulation   PT PTT Date Sec Sec 940119 14.3/12.2 32.6/28.9 4. Urine   Outlook PH Sp Gr Pro Bil Glu OB Uro K. B WBC RBC Epi Date       Mg/dL   G/dL   EU/dL   /HPF  /HPF  /HPF 940119 Y;C 7.0 1.014 - - - - 0.1 - 0-1  - 0-1 5. Microbiology lab 931209: Blood culture and sensitivity Salmonella group D (O9) for two sets Sensitive to ampicailline, ceftriaxone, cefotaxime, ciprofloxacin, floxacin, levofloxacin, SXT, ZOX, 6. Stool Date Appearance OB 940124 YB;F  - < CXR> 94.01.19 Cardiomegaly. Calcification of the aortic knob. The contour of the lower thoracic aorta is blurred. Blunted left CP angle. <ECG>94.01.19 Sinus rhythm, rate 83 beats/min; first degree AV block; RBBB. <Echocardiography & color duplex>94.01.19 AO 29 mm   IVS       10 mm   LVEF M-mode 65% AV 16 mm   LVPW  11 mm LA 29 mm   LVEDD 52 mm   LV mass 244 gm                    LVESD  33 mm Good LV contractility Probable LV diastolic dysfunction MR , mild TR, mild, PG 26 mmHg Minimal pericardial effusion, with no RA/RV diastolic collapse sign <CT scan>saccular aneurysm <CT scan>aortic dissection Chest, abdomen CT without/with enhancement showed Aortic dissection with intimal flap from aortic arch to descending thoracic aorta is noted. Partial mural thrombus in the false lumen with extension upward into proximal left subclavian artery is also found. Calcification at the orifice of left common carotid artery is noted. Aneurysmal dilatation of descending thoracic aorta, diameter up to 5cm, with enhancement of descending thoracic aorta and small hypodensity at periaortic region. There is mild bilateral left pleural effusion with partial atelectasis at left basal lung. No definite mediastinal LAP; no definite nodular lesion or consolidation in both lungs; no definite lesion in liver, GB, spleen, pancreas, both kidneys and adrenal glands. <Discussion> Salmonella are widely distributed in nature in a range of animal hosts and are strongly associated with agricultural products. More than 95% of cases of Salmonella infection are food born. Virtually any anatomical site maybe seeded hematogenously by non-typhoidal Salmonella, but only a minority of bacteremic patients will develop focal metastatic infections of the bones, meninges, brain, lung, abdominal viscera, and cardiovascular system. Risk factors of salmonellosis include extreme of age, diabetes, malignancy, rheumatologic disorder, AIDS, SLE, gastric hypoacidity, alteration of endogenous bowel flora resulted from antimicrobial therapy or surgery. In contrast to most Gram-negative bacteria, Salmonella has the propensity to adhere to damaged endothelium of the heart and arterial walls. Cardiovascular infections due to Salmonella had the spectrum of mycotic aneurysm, pericarditis, endocarditis, AV fistula infection, and device related infections. Mycotic aneurysm is the most common endovascular infections caused by non-typhoidal Salmonella. Salmonella can infect preexisting aneurysms or atherosclerotic plaques and produce necrosis of the arterial wall, resulting in rapid formation of a mycotic pseudoaneurysm. Old age, diabetes mellitus, hypertension, and preexisting atherosclerotic disease are the predominant risk factors among these patients. The most frequent site involved is the abdominal aorta, especially infrarenal segment, followed by thoracic aorta. The clinical presentation is usually a subacute course of fever, chills, chest pain, back pain, or abdominal pain, with or without preceding diarrhea and abdominal cramping pain. According to the infected site, there may be pulsatile tender abdominal mass, psoas muscle or pelvic abscess, vertebral osteomyelitis, purulent pericarditis, empyema, hemoptysis or GI bleeding due to aortobronchial or aortoenteric fistula. Persistent or relapsing bacteremia after discontinuing antibiotics were important clues for the diagnosis of Salmonella aortitis. Diagnosis needs a high index of suspicion. In the elderly, fever and abdominal pain or chest pain with a history of diarrhea suggested the diagnosis. CT scan with contrast enhancement is the diagnostic tool of choice. Other modalities, such as MRI, angiography, Ga-67 scan, Tc-99m labeled leucocyte scan and TEE, were also useful diagnostic tools. Diagnostic features on CT scan include (1) a periaortic soft tissue density with rim enhancement, consistent with periaortic inflammation; (2) hematoma suggesting pseudoaneurysm formation; (3) an eccentric, saccular, thickened aorta wall without calcium; and (4) gas in the aneurysmal sac. Differentiation from atherosclerotic aneurysms depends on the nonfusiform appearance, atypical location and rapid progression. In the past, mycotic aneurysm had high mortality. Prognosis has significantly improved in the last 2 decades, from 69% mortality rate and common relapse before 1987 to 40% mortality rate currently. Early diagnosis, surgical intervention plus prolonged antibiotics therapy are essential for survival. Medical treatment only carries poor prognosis compared to surgical treatment plus prolonged antibiotics. In Hsu's series in our center, the 30-day, 90-day, and 1-year mortality rates were 3%, 12%, and 25%, respectively, in patients undertaking operation, and 45%, 59%, and 59%, respectively, in patients with no operation. In this case, medical treatment composes of prolonged effective antibiotics and standard treatment of aortic aneurysm and dissection. In our center, due to high prevalence of Salmonella resistance to ampicillin, the antibiotics regimen usually start with cefotaxime or ceftriaxone, which were proved to have higher in-vitro beta-lactamase stability. Aortic dissection involving the ascending aorta (Stanford type A; DeBakey type I or II) needs immediate surgical treatment. Surgical treatment of type A aortic dissection reduces the risk of poor outcomes (acute aortic insufficiency, tamponade, and neurologic sequelae) from progression of the dissection. Management of distal aortic dissection (Stanford type B; DeBakey type III) generally needs aggressive blood pressure control to target systolic pressure of 110 mmHg and pain control. The goal of medical treatment is to reduce shearing force (dP/dt) to the aortic wall. The recommended antihypertensives include intravenous s-blockers (metoprolol, propranolol, or labetalol) or in combination with vasodilating drugs such as sodium nitroprusside or angiotensin-converting enzyme inhibitors. Intravenous verapamil or diltiazem may also be used, especially if s-blockers are contraindicated. Among patients with type B dissection with medically uncontrolled pain and/or hypertension, or evidence of rupture or end organ involvement, surgical intervention should be emergently applied. In patients with a good response to antibiotic treatment, surgical intervention is considered after a complete course of antibiotic treatment for 4-6 weeks in the hospital. If symptoms such as fever, pain, shock and other possible complications related to aneurysm recur or newly develop, image study was followed. Emergent surgical intervention is considered for uncontrolled infection, evidence of impending rupture (severe pain, shock, large pseudoaneurysm for more than 5 cm). The surgical treatment includes wide debridement of necrotic tissue, copious saline irrigation, and in-situ graft reconstruction or extra-anatomic bypass. With combined treatment, in our center, the 30-day was 0%. The 90-day mortality rates were 0% for elective operation and 36% for non-elective operation. Advanced age, urgent surgery and medical treatment are associated with higher overall mortality. Post-operative antibioitc therapy is administered for at least 4 to 9 weeks in foreign series. In our center, the postoperative antibiotics is administered for 4 months and discontinued only when careful examination reveals no further signs of infection. <References>  Guerrero F, Manuel L. The spectrum of cardiovascular infections due to Salmonella enterica: a review of clinical features and factors determining outcome. Medicine 2004;83: 123-138. Nienaber CA, Eagle KA. Aortic dissection: new frontiers in diagnosis and management: Part I. Circulation 2003;108: 628–635. Nienaber CA, Eagle KA. Aortic dissection: new frontiers in fiagnosis and management: Part II. Circulation 2003;108: 772–778. Meerkin D, Yinnon AM, Munter RG, Shemesh O, Hiller N, Abraham AS. Salmonella mycotic aneurysm of the aortic arch: Case report and review. Clin Infect Dis 1995;21:523-528. Soravia-Dunand VA, Loo VG, Salit IE. Aortitis due to Salmonella: Report of 10 cases and comprehensive review of the literature. Clin Infect Dis 1999;29:862-868. Howe HS, Wong JSL, Ding ZP, Sivathasan C, Ang B, Koh WH, Feng PH. Mycotic aneurysm of a coronary artery in SLE-a rare complication of Salmonella infection. Lupus 1997;6:404-407. Nader R, Mohr G, Sheiner NM, Tampieri D, Mendelson J, Albrecht S. Mycotic aneurysm of the carotid bifurcation in the neck: Case report and review of the literature. Neurosurgery 2001;48:1152-1156. Carreras M, Larena JA, Tabernero G, Langara E, Pena JM. Evolution of salmonella aortitis towards the formation of abdominal aneurysm. Eur Radiol 1977;7:54-56. Hsu RB, Chen RJ. Infected aortic aneurysms: clinical outcome and risk factor analysis. J vas surg 2004;40:30-5. Wang JH, Liu YC, Yen MY, Wang JH, Chen YS, Wann SR, Cheng DL. Mycotic aneurysm due to non-typhi Salmonella: Report of 16 cases. Clin Infect Dis 1996;23:743-747. 繼續教育考題 1. (B) All of the following statements regarding chest pain are true except A Rapid evaluation of chest pain to identify life-threatening illness is important. Early identification of aortic dissection, AMI, pneumothorax and pulmonary embolism determines the prognosis. B Assessment involves a careful history, physical examination, and 12-lead ECG, chest roentgenogram. Biochemical tests, including cardiac enzyme, are essential for diagnosis and further triage decisions can’t be made without them. C Chest pain with constricting, squeezing or heaviness character, locating over substernum, radiating to left arm, shoulder, neck, jaw, with associated nausea, vomiting and diaphoresis suggests cardiac ischemic origin of chest pain. D Severe chest pain, with tearing, ripping or stabbing character and radiation to the back suggests aortic dissection. 2. (C) All of the following statements regarding aortic dissection are true except A Two classification schemes, Debakey and Stanford, based on anatomy are used currently, B  In addition to chest pain, congestive heart failure, AMI, syncope, CVA, paraplegia, and cardiac arrest could be the initial presentations of aortic dissection. C Pulse deficits, may be seen in up to 50% of cases and do not carry outcome impact. D All mechanisms weakening the aortic media layers can induce aortic dilatation and aneurysm formation, and eventually lead to intramural hemorrhage, aortic dissection, or rupture. Conditions such as long standing hypertension, Marfan syndrome, and Ehlers-Danlos syndrome are the examples. 3. (A) All of the following statements regarding the diagnosis of aortic dissection are true except A Virtually all cases of aortic dissection have abnormal chest roentgenogram. B CT scan, MRI, TEE/TTE and angiography can be the first diagnostic aid in establishing the diagnosis. C Modalities chosen should be based on local expertise and clinical availability rather than the published data, since each method has advantages and disadvantages. D CT scan and TEE offer the most rapid answer in most emergent situations. 4. (D) All of the following statements regarding the treatment of aortic dissection are true except  A Therapy of aortic dissection started from the differentiation of proximal ( type A) and non-proximal type of aortic dissection.  B Patients with suspected acute aortic dissection should be admitted to an intensive care or monitoring unit and undergo diagnostic evaluation immediately. C  Proximal aortic dissections mandate immediate surgical treatment. Patients with uncontrolled pain, hypertension, major branch vessel and end-organ involvement should also receive surgical intervention.  D Management of distal aortic dissection is generally started with medical treatment, including aggressive pain and blood pressure control with beta-blockers, calcium channel blockers, and hydralazine. 5. (D) Which of the statements below is true?  A Salmonella is a Gram-positive organism.  B Salmonella causes only gastrointestinal symptoms.  C Only immunocompromised patients pose the risk of salmonella bactermia.  D Emergence of drug-resistant Salmonella has become the major clinical problem. Resistance to extended spectrum cepholosporins and fluoroquinolone has been reported. 6. (C) Which of the statements below is not true?  A Salmonella species, Staphylococcus aureus, Pseudomonas and mycobacterium tuberculosis can be the pathogens of infected aneurysm.  B Old age, DM, hypertension and preexisting atherosclerotic disease are the feature of these patients of mycotic aneurysm caused by Salmonella  C Due to the uncommon incidence, we should not consider mycotic aneurysm as a possible cause in an elderly patient with prolonged chest pain, abdominal pain and fever  D Since AIDS is a risk factor of salmonellosis, AIDS patients rarely develop aortitis because they are younger and have no atherosclertic risk factors 7. (D) Considering mycotic aneurysm cause by Salmonella, which one is true?  A The most involved site is thoracic aorta followed by abdominal aorta. B  Except for aorta, no other arteries can be involved.  C You should never suspect mycotic aneurysm in a patient with fever, abdominal pain who denied preceding or concurrent diarrhea.  D Most patients with mycotic aneurysm caused by Salmonella presented with a subacute clinical picture with duration of symptoms ranging from 2 to 7 weeks; though fulminant cases do exist. 8. (B) For the diagnosis of mycotic aneurysm, which statement is not true?  A CT scan with contrast is the modality of choice.  B CT scan can absolutely detect the early change of aortitis, thus salmonella bacteremia with negative CT scan rule out the possibility of mycotic aneurysm.  C Angiography, Gallium scan, Tc-99m scan, TEE can be alternative diagnostic tool.  D Saccular aneurysm with periaortic inflammation signs is the diagnostic clue on CT scan 9. (B) For the treatment of mycotic aneurysm, which one is not true?  A Delayed diagnosis carried even more high mortality.  B Medical treatment is sufficient to control the infection and the weakened aortic wall will resolve after adequate infection control.  C For endovascular infection caused by Salmonella, third generation of cepholosporin is the better choice of initial regimen because of the proved better in-vitro beta-lactamase stability.  D Prolonged antibiotics after definitive treatment is mandatory. 10. (D) A 83-year-old male patient with DM, hypertension was diagnosed to have Salmonella related infective aneurysm over the proximal thoracic aorta, 3.0 cm in size with the presentations of fever, and abdominal pain. Initial CT study revealed no pseudoaneurysm, periaortic abcess or major branch involvement. He was treated with intravenous ceftriaxone 2g q12h. The fever subsided along with the leucocytosis and CRP level. One week later, he complained of aggravating chest pain. There was no new fever, focal neurologic deficit, new cardiac murmur, friction rub or unstable hemodynamics. The leucocytosis improved compared to previous study and no hemoglobin drop was noted. Chest roentgenogram revealed no mediastinal widening or accumulation of pleural effusion. The blood pressure under labetalol infusion was 128/70 mmHg. If you were his doctor, you should:  A Give adequate pain control only.  B Give pain control and lower the BP more aggressively.  C Since CT scan was just performed 7 days ago and obtain the diagnosis of uncomplicated aorta mycotic aneurysm of descending thoracic aorta in small size, there is no need to repeat the image study.  D Give pain control, lower the BP more aggressively and follow CT study since rapid progression of mycotic aneurysm can occur in one week or less. 答案解說 (B) Biochemical test can supply additional data, but the data are not available immediately, and triage decisions are made without them. Take acute myocardial infarction as an example, the elevation of cardiac enzyme usually take 4-6 hours to rise after onset. The time delay is an obstacle of appropriate diagnosis and timely treatment. (C) Pulse deficits carry an ominous sign heralding complications and bad outcome. (A) Chest roentgenogram is abnormal in 60% to 90% of cases of aortic dissection. Acute dissection, especially type A lesion, can present with a normal chest film. (D) Patients with suspected acute aortic dissection should be admitted to an intensive care or monitoring unit and undergo diagnostic evaluation immediately. Pain and blood pressure control to a target systolic pressure of 110 mm Hg can be achieved using morphine sulfate and intravenous s-blockers (metoprolol, propranolol, or labetalol) or in combination with vasodilating drugs such as sodium nitroprusside or angiotensin-converting enzyme inhibitors. Intravenous verapamil or diltiazem may also be used, especially if s-blockers are contraindicated. The aim of medical treatment is to reduce shearing force within the aorta; thus direct vasodilator with propensity of reflex tachycardia is not suitable for blood pressure control in cases of aortic dissection (D) Salmonella is Gram-negative, being a member of the family enterobacteriaciae. Salmonella causes gastrointestinal, cardiovascular, neuropsychiatric, respiratory and hematologic symptoms. Blood stream infection of Salmonella is more likely to occur in immunocompromised patients, but is also found in immunocompetent patients. (C) The number of reports of mycotic aneurysm was 150 till 1999. However, with the aging population, prevalence of risk factors of atherosclerosis and the well-established Salmonella in nature, potential of salmonella spreading with modern practices of food production, the possibility of salmonella related infective aneurysm should be always kept in mind in an elderly patient with prolonged chest pain, abdominal pain and fever. (D) The most frequent site involved is the abdominal aorta, more precisely its infrarenal segment, followed by the thoracic aorta. Other arteries, such as the iliac, popliteal, carotid, and coronary arteries, can on occasion be involved. (B) It must be taken into account that when Salmonella infects atherosclerotic plaques, CT scan and even aortography do not detect the early changes produced in the arterial wall or in the periaortic tissue. Evolution of Salmonella aortitis to the formation of a mycotic aneurysm is, however, a rapid process that takes 1 week or less, so subsequent CT scans may exhibit the definitive signs of arterial infection. (B) In series of Hsu, 30-day, 90-day, and 1-year mortality rates were 3%, 12%, and 25%, respectively, in patients receiving operation, and 45%, 59%, and 59%, respectively in patients not operated. Treatment with antibiotics alone, aortitis due to Salmonella was uniformly fatal. (D) Combined medical and surgical treatment is recommended. Among patients with a good response to antibiotic treatment (no fever, declining white blood cell count), surgical intervention is considered after a complete course of antibiotic treatment for 4 to 6 weeks in the hospital and the infection is controlled. Imaging studies should be repeated if new symptoms (recurrent fever, pain, shock) develop or after complete antibiotic treatment. Early surgical intervention, which is defined as operation before 4 to 6 weeks of antibiotic treatment, should be performed in patients with uncontrolled infection (persistent fever, septic shock) or evidence of impending aortic rupture (severe pain, shock, large pseudoaneurysm formation on imaging studies).